The prevalence of diabetes is rising rapidly worldwide, and certain developing nations are currently going through an upsurge of type 2 diabetes of epidemic proportions.1
This is likely to have huge socio-economic consequences for healthcare resources in these countries due to considerable expense associated with complications of type 2 diabetes. 2 Primary prevention of type 2 diabetes is, therefore, of particular interest to health economists as it has in-built secondary and tertiary prevention of complications related to diabetes. This chapter is not meant to be a comprehensive review of the prevention of diabetes, but will deal mostly with the results of recently published randomized trials, which have used lifestyle intervention, including physical activity, to reduce or prevent type 2 diabetes.
However, we must remember that these studies were performed in subjects at high risk of future diabetes and not in those with normal glucose tolerance. Therefore, findings of these trials may not be applicable to the population at large. Therefore, in any community-based or public health approach to prevent diabetes and related diseases such as coronary heart disease, this is important for effective utilization of resources.
Type 2 diabetes has a number of disease characteristics which make it potentially a preventable disease.3,4 Considerable knowledge exists about risk factors for diabetes which are potentially modifiable.5 Although there is a strong genetic predisposition to this disease, environmental factors play an important role in the development of clinical diabetes. It is also clear that both insulin resistance and defective insulin secretion contribute to the development of diabetes, although the relative contribution of each of these two components varies in different populations and individuals within a population. 6-8
In most subjects predisposed to develop type 2 diabetes, there is generally a long but variable period during which minor degree of glucose intolerance exists.9-12 This stage of pre-diabetes can be recognized by performing an oral glucose tolerance test and is known as impaired glucose tolerance (lGT). It can also be diagnosed by measuring fasting plasma glucose, known as impaired fasting glucose (IFG).13·1 Subjects thus identified are at a higher risk of future diabetes compared with those whose glucose tolerance is normal.9-12 Identification of subjects at high risk of diabetes provides us with an opportunity to modify the disease process, either to delay or prevent it from becoming clinically manifest.
As in type 2 diabetes, insulin resistance and defective insulin secretion contribute to the development of lGT and IFG. Both of these defects can be modified through lifestyle interventions and/or pharmacological therapies.3 In spite of this, it has only recently been shown that type 2 diabetes can be prevented.13 Behavior modification through diet and exercise are attractive and have the added advantage of modifying other associated conditions such as coronary artery disease, hypertension and obesity.16 However, lifestyle modifications are extremely difficult to sustain over the lifetime of a given individual. In addition, it is likely that different strategies may need to be adopted in different ethnic groups to improve adherence to measures which will promote healthy lifestyles. 17
It has been known for some time that physical inactivity is associated with increased risk of type 2 diabetes. The results of various epidemiological and observational studies are summarized in Table 4.1 and showed that regular physical activity had a protective effect on the development of type 2 diabetes. These studies were remarkable for their consistent findings in the protective effects of physical activity on the occurrence of type 2 diabetes. In addition, some of the studies also showed a dose-response relationship between the frequency of physical activity and the degree of protective effect.15-22 These studies suggested a causative role for physical inactivity in type 2 diabetes.
Table 4.1 Prospective studies of physical activity and risk of type 2 diabetes
In the Physician Health Study published by Manson et al.,18 21,271 males were followed over a 5 year period. In this study, the incidence of diabetes was negatively related to the frequency of exercise (369 cases per 100 000 person-years in those who exercised less than once a week and 214 in those who exercised more than five times a week). The age-adjusted risk of diabetes in men who exercised at least once a week was 0.64 compared to those who exercised less frequently. The protective effect of exercise was unrelated to baseline body mass index (BMI) and was more marked in obese subjects.
In the study by Helmrich et al.,19 type 2 diabetes was observed in 202 subjects out of 5,990 male subjects. In this study, leisure time physical activity, expressed as number of calories expended was found to be inversely related to the development of diabetes. The age-adjusted risk of diabetes was 6 per cent lower for each 500 kcal expended. These beneficial effects of exercise remained significant when adjusted for the confounding effects of obesity, blood pressure and parental history of diabetes.
In the Nurses’ Health Study, women who participated in vigorous physical activity at least once a week had a 33 per cent lower risk of diabetes compared with those who did not take part in such activities.20 No dose-response relationship between frequency of exercise and risk of diabetes was seen in this study.
In the Honolulu Heart Study, subjects were followed for a period of 6 years and the cumulative incidence of diabetes was lower with increasing levels of physical activity in both men and women.21 The age-adjusted odds ratio for diabetes comparing subjects who were in the upper quintile with those in the lower four quintile was 0.55 for men and 0.50 in women, i.e. in both men and women in the highest quintile of physical activity the risk of diabetes was approximately half compared with the rest.
A study recently published by Lynch et al., 22in 897 middle-aged Finnish men, showed that, self-reported moderate intensity exercise undertaken for 40 min per week was associated with 56 per cent lower risk of type 2 diabetes. They also found that high levels of cardiorespiratory physical fitness (02 consumption in a respiratory chamber) also had a protective effect on the development of diabetes. In subjects who were at high risk of diabetes, with even a moderate degree of physical activity taken once a week for more than 40 min, the risk of diabetes was 64 per cent lower than those who did not take part in physical activity.
These studies were observational and formed the basis for conducting well-designed, randomized clinical trials to assess the effects of interventions incorporating physical activity on future development of type 2 diabetes. The major concern in the use of lifestyle intervention to prevent diabetes has been around the issue of long-term sustainability of this intervention. The study by Eriksson et al.,23 which is discussed in Chapter 5, showed that it was possible for subjects to comply with a behavior modification for up to 6 years, with good outcomes even after a 12 year follow-up.
These major intervention trails published over the last few years are summarized in Table 4.2. The Da-Qing study from China was the first population-based randomized study. In this study 576 subjects with IGT were randomized as to diet alone, exercise alone or both and had a control group with no intervention. Subjects were followed for an average period of 5.6 years. The incidence diabetes was reduced in all three intervention groups and to an equal extent with 50 per cent reduction in the incidence of diabetes (Table 4.3). Some general points of interest emerged from this study. 15
- Lifestyle Interventions in the form of diet and physical activity for up to 6 years significantly reduced the development of diabetes.
- The effects of diet or exercise were similar, i.e. both reduced the risk of diabetes.
- The effects were similar in obese and non-obese subjects.
- The risk of diabetes was reduced despite fairly modest reduction in body weight (approximately 2 kg).
- The increase in physical activity was modest but was sustained over the lifetime of the study
The results of a recently published Diabetes Prevention Study (DPS) study from Finland have been extremely encouraging.25 In this study the authors studied 522 subjects (172 men, 350 women). These were middle-aged subjects with a mean age of 55 and with a mean BMI of 31. Intervention in the control group consisted of verbal and written instructions about diet and exercise at baseline. The intervention group was given individualized dietary counseling aimed at reducing weight, total fat and saturated fat intake and increasing intake of fiber. This intervention was given in one-to-one sessions with the dietician seven times during the first year and 3 monthly thereafter. Physical activity counseling was also individually designed. It included both aerobic and resistance training, and increased walking with routine daily activities was encouraged. Some supervised activities were provided to train people. An oral glucose tolerance test (OGTT) was given annually on all subjects. If abnormal, diabetes was confirmed by a second OGTT test.
After an average follow-up of 3.2 years, subjects in the intervention group lost 4.2 kg of weight compared with 0.8 kg in the control group at year 1 with 3.5 and 0.8 kg at year 2, respectively. The cumulative incidence of diabetes in the intervention group was 11 per cent (95 per cent confidence interval, CI, 6-15) compared with 23 per cent (95 per cent CI 17-29) in the control group. Therefore, lifestyle intervention resulted in a total risk reduction of 58 per cent, results which were highly significant. Furthermore, the reduced incidence of diabetes was related to lifestyle changes. To interpret data in another way, 22 subjects with IGT will need to be treated for a year (or five subjects for 5 years) in this way to prevent one case of diabetes.
In the Diabetes Prevention Project (DPP) from the USA, 3,234 subjects at high risk of type 2 diabetes were recruited. Eligibility criteria included age greater than 25 years, minimal overweight and IGT as defined by WHO criteria. This study included 68 per cent women and 45 per cent of subjects were non-Caucasian (African-American, Hispanic, American Indians and Asian-Americans). The mean age was 51 years and BMI was 34 kgm. Subjects were randomized to intensive lifestyle interventions (n = 1979), placebo (n = 1082) and metformin 850 mg twice daily (n = 1073). Intervention consisted of a goal of losing 7 per cent of weight and at least 150 min of exercise per week. The participants in the intensive exercise program met case study managers on a one-to-one basis 16 times during the first 6 months and monthly thereafter. Primary outcome was diabetes based on results of an OGTT. The results of this study confirmed that type 2 diabetes could be prevented by lifestyle modifications and by pharmacological interventions. The risk of diabetes was reduced by both lifestyle changes in the form of diet and exercise and also by metformin treatment. After an average follow-up of 2.8 years the incidence of diabetes was 11.0, 7.8, 4.8 cases per 100 person-years of follow-up in placebo, metformin and lifestyle interventions, respectively. The lifestyle intervention reduced diabetes incidence by 58 per cent and metformin by 38 percent compared with placebo treatment.26
The findings of protective effect of lifestyle or metformin on diabetes were similar in men and women and in all racial groups. In general, lifestyle interventions were equally effective irrespective of age or gender. They were more advantageous in older people with a lower body mass index, compared with younger persons and those with higher body mass index. Of major interest were the findings that both lifestyle intervention and metformin were similarly effective in restoring fasting glucose, but lifestyle intervention was more effective restoring post-load glucose values.
In addition to these three landmark trials, other studies to prevent diabetes populations at high risk but using pharmacological interventions are worth considering briefly. In the STOP-NIDDM study, acarbose was evaluated in a placebo controlled trial in subjects with IGT.27 After a mean follow-up of 3.3 years, the absolute risk reduction was 9 per cent in acarbose group and relative risk was reduced by 36 per cent when diabetes was confirmed with a second OGTT. In addition, in subjects with IGT there was a significant reversion to NGT.
In the TRIPOD study, 236 Hispanic women with gestational diabetes were randomized to troglitazone which has now been withdrawn from the market. After a follow-up of 2.5 years, the incidence of diabetes was 12.3 and 5.4 per cent control and intervention groups giving a relative risk reduction of 56 per cent In future progression to diabetes.28
The results of the XENDOS trial have been published in which orlistat and lifestyle intervention reduced risk of diabetes by 37 per cent compared with lifestyle alone. Another major consideration was that the orlistat group had significant reduction in cardiovascular risk factors. These results underscore the fact that obesity prevention with whatever measures is needed to reduce diabetes and cardiovascular risk.29 Other drugs especially angiotensin-converting enzyme inhibitors (ACE-I) appear to be promising in preventing new-onset diabetes in a number of studies such as the HOPE and LIFE trials.30,31 Studies are in progress (DREAtv1, NAVIGATOR) which will assess the impact of ramipril, rosiglitazone and the insulin secretagogue nateglinide on incident diabetes.32,33
The cost of interventions used in the DPS and DPP has been assessed in French, German and UK set-ups,34 and was found to be higher for lifestyle intervention than for metformin. This should not come as a surprise, considering the huge cost of interventions which are needed for behavior change so that one can adopt and maintain positive changes in lifestyle. Therefore, it might be argued that pharmacological interventions may appear to be a more attractive option for preventing diabetes. However, lifestyle interventions have the potential to impact multiple disease states. Diabetes prevention is a major public health issue in populations with high prevalence of type 2 diabetes, such as Asian Indians, as the rates of diabetes are projected to double over the next 20 years.1 It remains for the health policy makers to make this a public health issue and urgent intervention trials are needed in these populations. The results of the Diabetes Prevention Trial in the Indian population are currently underway and we await the results with eagerness. However, lifestyle interventions in different racial groups may be particularly challenging17 suggesting that, when intervening with lifestyle measures, different strategies may need to be adopted in different racial groups. In a study reported from Tanzania in people of Hindu religion, simple dietary advice to eat less and exercise more in the form of walking for 30 min per day, resulted in protection from progression to diabetes.32-33
In most studies of lifestyle interventions, there was a tendency towards a reduction in risk factors for cardiovascular disease such as total and LDL-cholesterol and triglyceride and a decrease in systolic and diastolic blood pressure. There are few studies reported or in progress to date which will address the issue of whether treatment of IGT leads to prevention of cardiovascular disease. A high priority is not only to prevent or delay the onset of diabetes, but to reduce the future risk of macrovascular disease as well so that excess morbidity and mortality from manifestations of cardiovascular disease can be reduced. The STOP-NIDDM trial showed reversion to normal glucose tolerance in 30 per cent of subjects and a reduced risk of cardiovascular events. The long-term follow-up of DPP and DPS cohorts is awaited to see if interventions in these studies will result in reductions in long-term mortality from cardiovascular disease.
There would appear to be a greater urgency to develop strategies to prevent type 2 diabetes, given that diabetes seems to be appearing at a younger and younger age and in some countries in children and adolescents.36 On the other hand, for the results of clinical trials to prevent diabetes to be meaningful, the results need to be generalizable, but the methods need to be affordable, practical and acceptable so that these can be easily implemented. It is quite clear that the intensity of intervention in the trials is not affordable even in the rich countries. 37
In relation to the prevention of diabetes and coronary heart disease in the population at large, the following conclusions and recommendations may seem logical:
- Increase physical activity in the population at large by low-cost, low-key, but effective interventions (population approach).
- More intensive intervention should be aimed at those at high risk and a strategy is needed to identify these individuals (high risk approach).
Those who are at high risk may need to be categorized in terms of the preference and ability to comply with various interventions so that intervention can be targeted. This may be crucial for the cost-effective utilization of resources, as some people may not choose to or be able to increase physical activity and therefore, may rely predominantly on dietary and/or pharmacological manipulations.
In a given population both approaches will be required to complement each other, as interventions in high-risk people are more likely to be successful if all the population is geared to some sort of low-key interventions. However, this would need a clear and effective strategy to identify those at high risk by easy and effective means to target intervention.
- King H. Aubert R. Herman W. Global burden of diabetes 1995-2025. Prevalence, numerical estimates, and projections. Diabet Care 1998; 21: 1414-143l.
- Greener M, Counting the cost of diabetes. Costs Options Diabet 1997; 10: 4-5.
- Knowler We. Narayan KMY, Hanson RL, Nelson RG. Bennett PH, Tuommilehto Schersten B, Pettitt DJ. Perspective in diabetes. Preventing non-insulin-dependent diabet: Diabetes 1995; 44: 483-488.
- Tuommilehto J, Knowler We. Zimmet P. Primary prevention of non-insulin-dependdiabetes. Diabetesllyletab Rev 1992: 8: 339-353.
- Bennett PH. Impaired glucose tolerance – a target for intervention? Arteriosclerosis 1985:315-317.
- De Fronzo RA. Pathogenesis oftype 2 (non-insulin dependant) diabetes mellitus: a balance overview. Diabetologia 1992; 35: 389-397
- Turner Re. Holman RR. Mathews DR. Peto J. Relative contributions of insulin deficiency and insulin resistance in maturity-onset diabetes. Lancet 1982; i: 596-598.
- Gerich JE, Role of insulin resistance in the pathogenesis of type 2 (non-insulin dependence diabetes mellitus. Ciin Endocrinoll’v1etab 1988: 2: 307-326.
- Nagi DK, Knowler We. Charles MA, Lui QZ, Hanson RL McCance DR, Pettitt DJ, BenL PH. Early and late insulin response as predictors of NIDDM in Pima Indians with impaired glucose tolerance. Diabetologia 1995; 38: 187-192.
- Saad ME Knowler We. Pettitt DJ. Nelson RG, Mott DG, Bennett PH. The natural history
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- Kadowaki T. Miyaki Y. Hagura R. Akanuma Y. Kuzuya N. Takaku E Kosaka K. Risk fact for worsening to diabetes in subjects with impaired glucose tolerance. Diabetologia 19′- 26: 44-49.
- King H, Zimmet P, Raper LR, Balkau B. The natural history of impaired glucose tolerance in the micronesian population of Nauru: a 6 year follow-up study. Diabetologia 1984; 26: 39-:
- World Health Organization. Definition. Diagnosis and Classification of Diabetes Mellitusand its complications. Part 1: Diagnosis and classification of Diabetes Mellitus. Report – WHOINCDINCS/99.2. Geneva: Department of Non-Communicable Disease Surveillance WHO. 1999.
- Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus Diabetes Care 1998; 21 (suppl. 1): S5-S19.
- Pan X, Li G, Hu Y, Yang W, An Z, Hu Z, Lan J, Xiao J-Z, Cato H. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. Diabet Care 1997; 20: 537-544.
- King H, Kriska AM. Prevention of type 2 diabetes by physical training. Diabet Care 1992; 15: 1794-1799.
- Narayan KMV, Hoskin M, Kozak D, Kriska A, Hanson RL, Pettitt DJ, Nagi DK, Bennett PH, Knowler WC. Randomised clinical trial of life style interventions in Pima Indians-a pilot study. Diabet Med 1998; 15: 66-72.
- Manson JE, Rimm RB, Stamfer MI, Colditz GA, Willet WC, Krolewski AS, Rosner B, Hennekens CH, Speizer FE. A prospective study of exercise and incidence of diabetes among US male physicians. lAMA 1992; 268: 63-67.
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- Manson JE, Rimm RB, Stamfer MJ, Colditz GA, Willet WC, Krolewski AS, Rosner B, Hennekens CH, Speizer FE. Physical activity and incidence of non-insulin-dependent diabetes in women. Lancet 1991; 338: 774-778.
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- Lynch J. Helmrich, Moderately intense physical activity and high levels of cardiorespiratory fitness reduce risk of Non-insulin diabetes. Arch Intern Med. 1996 156: 1307-1314
- Eriksson KF, Lindgarde F. No excess 12-year mortality in men with impaired glucose tolerance who participated in Malmo preventive trail with diet and exercise. Diabetologia 1998; 41: 1010-1017.
- Frisch RE, Wyshak G, Albright TE, Albright NL, Schiff 1. Lower prevalence of diabetes in female former college athletes compared with non-athletes. Diabetes 1986; 35: 1101-1105.
- Tuomilehto J, Lindstrom J, Eriksson JG. Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaannierni S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New Eng/ 1 Med 2001: 344: 1343-1350.
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- Chiasson JL, Josse RG, Gomis R. Hanefield :tvl, Karasik A. Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002; 359: 2072-2027.
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- Heart Outcomes Prevention Evaluation (HOPE) Study. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE sub study. Lancet 2000: 355: 253-259.
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Copyright © 2010 by Blackwell Publishing Ltd, UK
Fully updated to reflect the progress and understanding in the field, the book features new chapters and material on insulin pump therapy and exercise, physical activity and prevention of type 2 diabetes, dietary advice for exercise and sport in type 1 diabetes, and fluid and electrolyte replacement.
For more information on this book and how to get a copy, just follow this link to Amazon.com, Exercise and Sport in Diabetes (Practical Diabetes), Dinesh Nagi 2nd Edition.